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Tryptophan metabolism in depressive illness

Published online by Cambridge University Press:  09 July 2009

Alec Coppen
Affiliation:
Medical Research Council Neuropsychiatry Unit, West Park Hospital, Epsom, and Carshalton, Surrey
Benjamin W. L. Brooksbank
Affiliation:
Medical Research Council Neuropsychiatry Unit, West Park Hospital, Epsom, and Carshalton, Surrey
Eric Eccleston
Affiliation:
Medical Research Council Neuropsychiatry Unit, West Park Hospital, Epsom, and Carshalton, Surrey
Malcolm Peet
Affiliation:
Medical Research Council Neuropsychiatry Unit, West Park Hospital, Epsom, and Carshalton, Surrey
Stuart G. White
Affiliation:
Medical Research Council Neuropsychiatry Unit, West Park Hospital, Epsom, and Carshalton, Surrey

Sysnopsis

[Methylene-14C]-L-tryptophan was administered intravenously to five patients suffering from severe depression before and after clinical recovery, and to six control subjects; all subjects were tested while on a standard diet. [14C]-5-Hydroxyindoleacetic acid and [14C]-indoleacetic acid were isolated from urine during the following 48 hours and purified to constant specific radioactivity (SA). From the SA and the determination of the total excretion of the two acids their percentage conversion from labelled tryptophan was estimated. There was no consistent difference found, in patients before and after recovery, or between patients and controls, in the conversion of tryptophan to these indole acids. In another series of 11 depressive patients and 11 controls, plasma total (acid-soluble) tryptophan was measured at frequent intervals up to three hours after intravenous administration of a loading dose (1 g) of L-tryptophan. The height of the curves of plasma tryptophan throughout the three hour period was greater than in the depressive patients, even after they had recovered, than in the controls. It is concluded that the apparent volume of distribution of tryptophan is reduced in depressive individuals. This is consistent with other findings of increased protein-binding of plasma tryptophan and reduced CSF tryptophan levels in depressive patients.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1974

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References

REFERENCES

Armstrong, M. D., Shaw, K. N. F., Gortatowski, M. J., and Singer, H. (1958). The indole acids of human urine. Paper chromatography of indole acids. Journal of Biological Chemistry, 232, 1730.CrossRefGoogle ScholarPubMed
Ashcroft, G. W., Crawford, T. B. B., Eccleston, D., Sharman, D. F., MacDougall, E. J., Stanton, J. B., and Binns, J. K. (1966). 5-Hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological diseases. Lancet, 2, 10491052.CrossRefGoogle ScholarPubMed
Ayuso Gutierrez, J. L., and López-Ibor Aliño, J. J. (1971). Tryptophan and an MAOI (nialamide) in the treatment of depression. International Pharmacopsychiatry, 6, 9297.CrossRefGoogle Scholar
Benassi, C. A., Benassi, P., Allegri, G., and Ballarin, P. (1961). Tryptophan metabolism in schizophrenic patients. Journal of Neurochemistry, 7, 264270.CrossRefGoogle Scholar
Berkowitz, B. A., and Spector, S. (1971). The effect of caffeine and theophylline on the disposition of brain serotonin in the rat. European Journal of Pharmacology, 16, 322325.CrossRefGoogle ScholarPubMed
Bourne, H. R., Bunney, W. E. Jr., Colburn, R. W., Davis, J. M., Davis, J. N., Shaw, D. M., and Coppen, A. J. (1968). Noradrenaline, 5-hydroxytryptamine, and 5-hydroxyin-doleacetic acid in hindbrains of suicidal patients. Lancet, 2, 805808.CrossRefGoogle Scholar
Bowers, M. B. Jr. (1972). Clinical measurements of central dopamine and 5-hydroxytryptamine metabolism: reliability and interpretation of cerebrospinal fluid acid monoamine metabolite measures. Neuropharmacology, 11, 101111.CrossRefGoogle ScholarPubMed
Broadhurst, A. D. (1970). 1-Tryptophan versus E.C.T. Lancet, 1, 13921393.Google Scholar
Burgermeister, J.-J., Dick, P., Garonne, G., Guggisberg, M., and Tissol, R. (1963). Excrétion urinaire de l'acide 5-hydroxyindolacétique (5-HIAA) chez 150 malades atteints de syndrome dépressif et d'agitation maniaque. (Ses modifications par surcharge de 5-hydroxytryptophane, et par la thérapeutique chez les dépressifs). Presse Médicale, 71, 11161118.Google Scholar
Carroll, B. J. (1971). Monoamine precursors in the treatment of depression. Clinical Pharmacology and Therapeutics, 12, 743761.CrossRefGoogle ScholarPubMed
Cazzullo, C. L., Mangoni, A., and Mascherpa, G. (1966). Tryptophan metabolism in affective psychoses. British Journal of Psychiatry, 112, 157162.CrossRefGoogle ScholarPubMed
Chiancone, F. M., and Bonollo, L. (1969). Fumo di tobacco, nicotina e metabolismo del triptofano. Acta Vitamino-logica et Enzymologica, 23, 103110.Google Scholar
Contractor, S. F. (1966). A rapid quantitative method for the estimation of 5-hydroxyindoleacetic acid in human urine. Biochemical Pharmacology, 15, 17011706.CrossRefGoogle Scholar
Coppen, A., Brooksbank, B. W. L., and Peet, M. (1972). Tryptophan concentration in the cerebrospinal fluid of depressive patients. Lancet, 1, 1393.CrossRefGoogle ScholarPubMed
Coppen, A., Eccleston, E. G., and Peet, M. (1972). Total and free tryptophan concentration in the plasma of depressive patients. Lancet, 2, 14151416.CrossRefGoogle ScholarPubMed
Coppen, A., Eccleston, E. G., and Peet, M. (1973). Total and free tryptophan concentration in the plasma of depressive patients. Lancet, 2, 6063.CrossRefGoogle ScholarPubMed
Coppen, A., Prange, A. J. Jr., Whybrow, P. C., and Noguera, R. (1972). Abnormalities of indoleamines in affective disorders. Archives of General Psychiatry, 26, 474478.CrossRefGoogle ScholarPubMed
Coppen, A., Shaw, D. M., and Farrell, J. P. (1963). Potentiation of the antidepressive effect of a monoamine-oxidase inhibitor by tryptophan. Lancet, 1, 7981.CrossRefGoogle ScholarPubMed
Coppen, A., Shaw, D. M., Herzberg, B., and Maggs, R. (1967). Tryptophan in the treatment of depression. Lancet, 2, 11781180.CrossRefGoogle ScholarPubMed
Coppen, A., Shaw, D. M., and Malleson, A. (1965a). Changes in 5-hydroxytryptophan metabolism in depression. British Journal of Psychiatry, 111, 105107.CrossRefGoogle ScholarPubMed
Coppen, A., Shaw, D. M., Malleson, A., Eccleston, E., and Gundy, G. (1965b). Tryptamine metabolism in depression. British Journal of Psychiatry, 111, 993998.CrossRefGoogle ScholarPubMed
Coppen, A., Whybrow, P. C., Noguera, R., Maggs, R., and Prange, A. J. Jr. (1972). The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation by liothyronine. Archives of General Psychiatry, 26, 234241.CrossRefGoogle ScholarPubMed
Curzon, G. (1969). Tryptophan pyrrolase—a biochemical factor in depressive illness? British Journal of Psychiatry, 115, 13671374.CrossRefGoogle ScholarPubMed
Curzon, G., and Bridges, P. K. (1970). Tryptophan metabolism in depression. Journal of Neurology, Neurosurgery and Psychiatry, 33, 698704.Google ScholarPubMed
Curzon, G., Friedel, J., and Knott, P. J. (1973). The effect of fatty acids on the binding of tryptophan to plasma protein. Nature, 242, 198200.CrossRefGoogle ScholarPubMed
Dencker, S. J., Malm, U., Roos, B.-E., and Werdinius, B. (1966). Acid monoamine metabolites in cerebrospinal fluid in mental depression and mania. Journal of Neurochemistry, 13, 15451548.CrossRefGoogle ScholarPubMed
Denckla, W. D., and Dewey, H. K. (1967). The determination of tryptophan in plasma, liver, and urine. Journal of Laboratory and Clinical Medicine, 69, 160169.Google ScholarPubMed
Dunner, D. L., and Goodwin, F. K. (1972). Effect of L-tryptophan on brain serotonin metabolism in depressed patients. Archives of General Psychiatry, 26, 364366.CrossRefGoogle ScholarPubMed
Eccleston, D., Ashcroft, G. W., Moir, A. T. B., Parker-Rhodes, A., Lutz, W., and O'Mahoney, D. P. (1968). A comparison of 5-hydroxyindoles in various regions of dog brain and cerebrospinal fluid. Journal of Neurochemistry, 15, 947957.CrossRefGoogle ScholarPubMed
Erspamer, V. (1966). Occurrence of indolealkylamines in nature. In Handbook of Experimental Pharmacology, Vol. 19, 5-Hydroxytryptamine and Related Indolealkylamines, pp. 132181. Edited by Eichler, O. and Farah, A.. Springer: Berlin.CrossRefGoogle Scholar
Fernstrom, J. D., and Wurtman, R. J. (1971). Brain serotonin content: physiological dependence on plasma trypto-phan levels. Science, 173, 149152.CrossRefGoogle Scholar
Fragoso Mendes, J. M., and Lopes do Rosario, J. A. (1959). Signification et importance de la sérotonine en psychiatrie. Encéphale, 48, 501509.Google Scholar
Glassman, A. H., and Platman, S. R. (1969). Potentiation of a monoamine oxidase inhibitor by tryptophan. Journal of Psychiatric Research, 7, 8388.CrossRefGoogle ScholarPubMed
Grahame-Smith, D. G. (1971). Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. Journal of Neurochemistry, 18, 10531066.CrossRefGoogle ScholarPubMed
Granowitz, E., and Pletscher, A. (1957). Die diagnostische Bedeutung der 5-Hydroxyindolessigsäure-Ausscheidung im Urin. Helvetica Medica Acta, 24, 2126.Google Scholar
Grizzle, J. E., and Allen, D. M. (1969). Analysis of growth and dose response curves. Biometrics, 25, 357381.CrossRefGoogle ScholarPubMed
Hagen, P. B., and Cohen, L. H. (1966). Biosynthesis of indolealkylamines. Physiological release and transport of 5-hydroxytryptamine. In Handbook of Experimental Pharmacology, Vol. 19, 5-Hydroxytryptamine and Related Indolealkylamines, pp. 182211. Edited by Eichler, O. and Farah, A.. Springer: Berlin.CrossRefGoogle Scholar
Jepson, J. B. (1969). Indoles and related Ehrlich reactors. In Chromatographic and Electrophoretic Techniques, Vol. 1, Chromatography, pp. 243273. Edited by Smith, I.. 3rd edn.Heinemann: London.Google Scholar
Jéquier, E. (1968). Tryptophan hydroxylation in phenyl-ketonuria. In Advances in Pharmacology, Vol. 6, Part B, pp. 169170. Edited by Garattini, S.. Academic Press: New York.Google Scholar
Jéquier, E., Lovenberg, W., and Sjoerdsma, A. (1967). Tryptophan hydroxylase inhibition: the mechanism by which p−chlorophenylalanine depletes rat brain serotonin. Molecular Pharmacology, 3, 274278.Google ScholarPubMed
Karoum, F., Anah, C. O., Ruthven, C. R. J., and Sandler, M. (1969). Further observations on the gas-chromatographic measurement of urinary phenolic and indolic metabolites. Clinica Chimica Acta, 24, 341348.CrossRefGoogle ScholarPubMed
Knott, P. J., and Curzon, G. (1972). Free tryptophan in plasma and brain tryptophan metabolism. Nature, 239, 452453.CrossRefGoogle ScholarPubMed
Knox, W. E. (1963). The adaptive control of tryptophan and tyrosine metabolism in animals. Transactions of the New York Academy of Sciences, Series 2, 25, 503512.CrossRefGoogle ScholarPubMed
Knox, W. E., and Auerbach, V. H. (1955). The hormonal control of tryptophan peroxidase in the rat. Journal of Biological Chemistry, 214, 307313.CrossRefGoogle ScholarPubMed
Knox, W. E., and Mehler, A. H. (1951). The adaptive increase of the tryptophan peroxidase-oxidase system of liver. Science, 113, 237238.CrossRefGoogle ScholarPubMed
Korf, J., and Valkenburgh-Sikkema, T. (1969). Fluorimetric determination of 5-hydroxyindoleacetic acid in human urine and cerebrospinal fluid. Clinica Chimica Acta, 26, 301306.CrossRefGoogle ScholarPubMed
Korf, J., Praag, H. M. Van, and Sebens, J. B. (1972). Serum tryptophan decreased, brain tryptophan increased and brain serotonin synthesis unchanged after probenecid loading. Brain Research, 42, 239242.CrossRefGoogle ScholarPubMed
Lapin, I. P., and Oxenkrug, G. F. (1969). Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. Lancet, 1, 132136.CrossRefGoogle ScholarPubMed
Leklem, J. E. (1971). Quantitative aspects of tryptophan metabolism in humans and other species: a review. American Journal of Clinical Nutrition, 24, 659672.CrossRefGoogle ScholarPubMed
Lipsett, D., Madras, B. K., Wurtman, R. J., and Munro, H. N. (1973). Serum tryptophan level after carbohydrate ingestion: selective decline in non-albumin-bound tryptophan coincident with reduction in serum free fatty acids. Life Sciences, 12, Part 2, 5764.CrossRefGoogle ScholarPubMed
McMenamy, R. H., and Oncley, J. L. (1958). The specific binding of L-tryptophan to serum albumin. Journal of Biological Chemistry, 233, 14361447.CrossRefGoogle ScholarPubMed
Maickel, R. P., Cox, R. H. Jr., Saillant, J., and Miller, F. P. (1968). A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. International Journal of Neuropharmacology, 7, 275281.CrossRefGoogle ScholarPubMed
Medical Research Council (1965). Clinical trial of the treatment of depressive illness. Report by its Clinical Psychiatry Committee. British Medical Journal, 1, 881886.CrossRefGoogle Scholar
Mendels, J., Frazer, A., Fitzgerald, R. G., Ramsey, T. A., and Stokes, J. W. (1972). Biogenic amine metabolites in cerebrospinal fluid of depressed and manic patients. Science, 175, 13801382.CrossRefGoogle ScholarPubMed
Michael, A. F., Drummond, K. N., Doeden, D., Anderson, J. A., and Good, R. A. (1964). Tryptophan metabolism in man. Journal of Clinical Investigation, 43, 17301746.CrossRefGoogle ScholarPubMed
Milne, M. D., Crawford, M. A., Girão, C. B., and Loughridge, L. W. (1960). The excretion of indolylacetic acid and related indolic acids in man and the rat. Clinical Science, 19, 165179.Google ScholarPubMed
Moir, A. T. B. (1971). Interaction in the cerebral metabolism of the biogenic amines: effect of intravenous infusion of L-tryptophan on tryptophan and tyrosine in brain and body fluids. British Journal of Pharmacology, 43, 724731.CrossRefGoogle ScholarPubMed
Moir, A. T. B., and Eccleston, D. (1968). The effects of precursor loading in the cerebral metabolism of 5-hydroxy-indoles. Journal of Neurochemistry, 15, 10931108.CrossRefGoogle Scholar
Pare, C. M. B. (1963). Potentiation of monoamine-oxidase inhibitors by tryptophan. Lancet, 2, 527528.CrossRefGoogle ScholarPubMed
Pare, C. M. B., and Sandler, M. (1959). A clinical and biochemical study of a trial of iproniazid in the treatment of depression. Journal of Neurology, Neurosurgery and Psychiatry, 22, 247251.Google ScholarPubMed
Pare, C. M. B., Yeung, D. P. H., Price, K., and Stacey, R. S. (1969). 5-Hydroxytryptamine, noradrenaline, and dopa-mine in brainstem, hypothalamus, and caudate nucleus of controls and patients committing suicide by coal-gas poisoning. Lancet, 2, 133135.CrossRefGoogle Scholar
Praag, H. M. Van, Korf, J., and Puite, J. (1970). 5-Hydroxy-indoleacetic acid levels in the cerebrospinal fluid of depressive patients treated with probenecid. Nature, 225, 12591260.CrossRefGoogle ScholarPubMed
Robins, E., Robins, J. M., Croninger, A. B., Moses, S. G., Spencer, S. J., and Hudgens, R. W. (1967). The low level of 5-hydroxytryptophan decarboxylase in human brain. Biochemical Medicine, 1, 240251.CrossRefGoogle Scholar
Roos, B.-E., and Sjöström, R. (1969). 5-Hydroxyindoleacetic acid (and homovanillic acid) levels in the cerebrospinal fluid after probenecid application in patients with manic-depressive psychosis. Pharmacologia Clinica, 1, 153155.CrossRefGoogle Scholar
Rubin, R. T. (1967). Adrenal cortical activity changes in manic-depressive illness. Influence on intermediary metabolism of tryptophan. Archines of General Psychiatry, 17, 671679.CrossRefGoogle ScholarPubMed
Schievelbein, H., Surberg, U., and Werle, E. (1962). Erhöhung der Ausscheidung von 5-Hydroxyindolessigsäure bei Rauchern. Klinische Wochenschrift, 40, 5253.CrossRefGoogle Scholar
Shaw, D. M., Camps, F. E., and Eccleston, E. G. (1967). 5-Hydroxytryptamine in the hind-brain of depressive suicides. British Journal of Psychiatry, 113, 14071411.CrossRefGoogle ScholarPubMed
Sprince, H., Parker, C. M., Jameson, D., and Josephs, J. A. Jr. (1969). Experimental alteration of tryptophan metabolism by methionine: neuropharmacologic implications. International Journal of Neuropharmacology, 8, 615626.CrossRefGoogle ScholarPubMed
Ström-Olsen, R., and Weil-Malherbe, H. (1958). Humoral changes in manic-depressive psychosis with particular reference to the excretion of catechol amines in urine. Journal of Mental Science, 104, 696704.CrossRefGoogle Scholar
Tagliamonte, A., Biggio, G., and Gessa, G. L. (1971). Possible role of “free” plasma tryptophan in controlling brain tryptophan concentrations. Rivista di Farmacologia e Terapia, 11, 251255.Google Scholar
Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., and Gessa, G. L. (1971a). Increase of brain tryptophan caused by drugs which stimulate serotonin synthesis. Nature New Biology, 229, 125126.CrossRefGoogle ScholarPubMed
Tagliamonte, A., Tagliamonte, P., Perez-Cruet, J., Stern, S., and Gessa, G. L. (1971b). Effect of psychotropic drugs on tryptophan concentration in the rat brain. Journal of Pharmacology and Experimental Therapeutics, 177, 475480.Google ScholarPubMed
Weissbach, H., King, W., Sjoerdsma, A., and Udenfriend, S. (1959). Formation of indole-3-acetic acid and tryptamine in animals. A method for estimation of indole-3-acetic acid in tissues. Journal of Biological Chemistry, 234, 8186.CrossRefGoogle ScholarPubMed